Does HCV Patients Who Have BCL2 43Ala Genotype and Normal GH1 Levels Can Achieve Response to IFN Based Therapy?

Eskander, Emad F.; Abdrabou, Ahmed; Mohamed, Mervat S.; Yahya, Shaymaa M. M.; Shaker, Olfat G.

doi:10.1007/s12291-012-0219-6

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…We compared the statistical relationship between the BCL2 gene (Ala43Thr) single-nucleotide polymorphism and growth hormone (GH1) levels in Egyptian HCV genotype-4 patients, both before and after treatment with PEG IFN plus ribavirin. The results showed that patients with HCV genotype-4 with normal GH1 concentration and the BCL-2/43Ala genotype could successfully achieve a response to IFN therapy [51]. We undertook to investigate the expression and relationship of the HCV core proteins -P21 and Bcl-2in tissues of patients with hepatitis C and cirrhosis; the positive expression of HCV core protein and mutant P21 is mainly located in the nucleus; for Bcl-2, the positive expression was mainly located in the cytoplasm; furthermore, the positive expression rate of P21 was only 13%, and the positive expression rate of Bcl-2 was 95.7%.…”

Section: Discussionmentioning

confidence: 98%

A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology

Zhang

Liu

et al. 2020

BMC Complement Med Ther

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Background Globally, more than 170 million people are infected with hepatitis C virus, a major cause of cirrhosis and hepatocellular carcinoma. The Yinchenhao Decoction (YCHD) is a classic formula comprising three herbal medicines. This decoction have long been used in China for clinically treating acute and chronic infectious hepatitis and other liver and gallbladder damp heat-accumulation disorders. Methods In this study, we identified 32 active ingredients and 200 hepatitis C proteins and established a compound-predicted target network and a hepatitis C protein–protein interaction network by using Cytoscape 3.6.1. Then, we systematically analyzed the potential targets of the YCHD for the treatment of hepatitis C. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by the Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses. Results This study adopted a network pharmacology approach, mainly comprising target prediction, network construction, module detection, functional enrichment analysis, and molecular docking to systematically investigate the mechanisms of action of the YCHD in hepatitis C. The targets of the YCHD in the treatment of hepatitis C mainly involved PIK3CG, CASP3, BCL2, CASP8, and MMP1. The module and pathway enrichment analyses showed that the YCHD had the potential to influence varieties of biological pathways, including the TNF signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and pathways in cancer, that play an important role in the pathogenesis of hepatitis C. Conclusion The results of this study preliminarily verified the basic pharmacological effects and related mechanisms of the YCHD in the treatment of hepatitis C.

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Section: Discussionmentioning

confidence: 98%

A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology

Zhang

Liu

et al. 2020

BMC Complement Med Ther

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“…Intriguingly, it was found that HCV genotype-4 patients who have normal growth hormone concentrations and BCL2 43Ala genotype can successfully achieve response to interferon-based therapy. 61 In addition, the hormonal profile (prolactin, total testosterone, growth hormone) provides promising biomarkers for HCV treatment response when associated with P53 rs1042522 and CD95 rs1800682 genetic polymorphisms; where sustained virological responders have low prolactin levels and either P53 rs1042522 C/C genotype or CD95 rs1800682 A/A genotype, high total testosterone concentrations and P53 rs1042522 C/C genotype, as well as high growth hormone levels and either P53 rs1042522 G/G genotype or CD95 rs1800682 A/A genotype compared to non-responders.…”

Section: Discussionmentioning

confidence: 99%

P53 rs1042522 and CD95 rs1800682 genetic variations in HCV-4a response to antiviral therapy

et al. 2015

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Current estimates indicate that the hepatitis C (HCV) is the leading cause of mortality around the world, with infection rates steadily increasing in Egypt. The dual therapy for this silent epidemic with pegylated-interferon-α2b/ribavirin has markedly improved the success rates in genotype-4 patients. It was reported that apoptosis plays a vital mechanistic role in limiting viral replication. P53, a key regulator of apoptosis, induces CD95 gene expression and subsequently initiates apoptotic cascade to be activated. The current study examined the impact of P53 rs1042522 and CD95 rs1800682 polymorphisms on the treatment response. Three groups of 240 volunteers were enrolled in this study; 86 in sustained virological responders group, 74 in non-responders group, and 80 in control group. All patients had HCV genotype-4a and were interferon treatment naïve. Quantizations of HCV-RNA by qRT-PCR and histological scores were performed for all patients. In addition, genotyping of HCV-RNA, P53 rs1042522 Arg/Pro and CD95 rs1800682 A/G polymorphisms were investigated in all subjects. It was resulted that P53 Pro/Pro homozygous genotype has high significant increase, while CD95 A/A homozygous genotype has high significant decrease when comparing non-responders with responders. Finally, it was concluded that Pro variant of P53 rs1042522 may be used as a genetic predictor for non-responsiveness, while A/A variant of CD95 rs1800682 may be used as a sensitive biomarker for responsiveness to antiviral therapy of HCV genotype-4a infection. In addition, low prolactin, high total testosterone, and high GH levels may provide promising biomarkers for early prediction of the response when associated with these genetic polymorphisms.

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“…Another very important factor which is powerfully involved as a pre-treatment predictor is the host gene. Various genetic polymorphisms of IL28B [18,19], 2 0 -5 0 -OAS [20], and BCL2 [21][22][23] were examined previously with the HCV response to the IFN-based therapy. These genetic polymorphisms provided good examples of pre-therapeutic host gene predictors for interferon response.…”

Section: Introductionmentioning

confidence: 99%

Correlation and Multiple Regression Analyses of Pituitary Growth Hormone and Hepatic Activities in Hepatitis C Infection and Interferon Response

et al. 2013

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The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest percent of infections reported in Middle East, increasingly in Egypt. The current study aimed at examining the bio-statistical correlation and multiple regression analyses of pituitary growth hormone (GH) and liver activities among HCV genotype-4 patients treated with PEG-IFN-a plus RBV therapy. Herein, the current study was conducted on 100 HCV genotype-4 infected patients and 50 healthy controls. Patients received PEG-IFN-a/RBV for 24 weeks. Host RNA was isolated from patients' sera for HCV genotyping and viral load determination. Moreover, the enzymatic activities of the liver, AFP, GH, PT, and CBC were performed in all volunteers. The present study resulted that the activities of the hepatic enzymes among HCV genotype-4 patients correlated together significantly. While, human GH showed a significant positive regression with pre-treatment ALT concentration in responders. Furthermore, multiple regression analysis for GH showed a significant positive correlation with pre-treatment ALT in HCV genotype-4 infected patients. We concluded that there were a putative significant relation between GH and pre-treatment ALT activity in HCV infection and response to IFN-based therapy.

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Does HCV Patients Who Have BCL2 43Ala Genotype and Normal GH1 Levels Can Achieve Response to IFN Based Therapy?

Cited by 3 publications

References 35 publications

A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology

A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology

P53 rs1042522 and CD95 rs1800682 genetic variations in HCV-4a response to antiviral therapy

Correlation and Multiple Regression Analyses of Pituitary Growth Hormone and Hepatic Activities in Hepatitis C Infection and Interferon Response

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